DESCRIPTION: (Applicant's Description) Inherited susceptibility to melanoma is genetically heterogeneous. Predisposing genes in some high risk families have been mapped by linkage analysis to chromosome arms 1p and 9p, while in other kindreds, there is no evidence for linkage to 1p or 9p. With the exceptions of mutations at the CDKN2A locus on 9p21 or the CDK4 locus on 12q13 in some families, the investigators understanding of inherited susceptibility to melanoma at the molecular level is limited. High-risk kindreds have been described in which involvement of known melanoma susceptibility loci have been excluded. The objective of this pilot study is to identify an additional locus governing melanoma susceptibility. A high-density genetic linkage analysis will be performed on lymphocyte DNAs from melanoma kindreds that have tested negative for linkage to markers on 1p and 9p or have no known CDKN2A or CDK4 mutations. The search will focus on chromosomes 3, 6, 10, 11, 16, and 21, which are the most likely locations of a novel melanoma susceptibility gene based on published cytogenetic, molecular, and genetic linkage studies. In collaboration with Margaret A. Tucker and Alisa M. Goldstein at the National Cancer Institute, linkage will be tested by considering the cutaneous malignant melanoma (CMM) trait alone, and the combined cutaneous malignant melanoma-dysplastic nevus (CMM/DN) trait. New information resulting from the proposed study will provide a basis for long-term studies aimed at the positional cloning and characterization of a melanoma susceptibility gene, which will further the understanding of the molecular basis of melanoma susceptibility and will suggest possible prevention strategies.